Type IV collagenase is an important basement membrane degrading metalloproteinase discovered by our laboratory. This enzyme is produced by malignant cells to facilitate their traversation through blood vessel walls as well as during transition from in situ to invasive carcinoma. Human type IV collagenase was isolated from culture supernatants of A2058 metastatic melanoma cells after four steps of purification. The collagenase has a molecular weight of 70 KDa and produced a typical cleavage pattern of type IV collagen by SDS gel electrophoresis. A second polypeptide was eluted off the collagen IV affinity column which has a molecular weight of 100 KDa. This new collagen IV binding protein has no collagenolytic activity and does not possess any characteristics of known matrix proteins. The control mechanism for type IV collagenase was studied in vitro in relation to attachment proteins such as laminin and fibronectin, as well as growth factors. The presence of laminin in the culture medium stimulated type IV collagenolytic activity of A2058 melanoma cells 200%, but fibronectin and BSA had no effect. The collagenase stimulating effect was mediated through the cell binding part of laminin, as demonstrated by the P-1 fragment of laminin which also was stimulatory (600%) when added to the culture supernatants. The stimulating effect was abolished by monoclonal antibodies to the laminin receptor, that specifically inhibit the cell binding site. In contrast to the laminin effect, three growth factors added to the A2058 culture supernatants inhibited the collagenase IV activity. The maximum inhibitory effect measured with EGF was 50%, FGF 43% and transferrin 30%. These in vitro studies show that production and/or secretion of type IV collagenase can be modulated by the cell binding fragment of the laminin molecule as well as by different growth factors.